Objective. Degeneration of extracellular matrix of cartilage leads to the production of molecules capable of activating the immune system via Toll-like receptor 4 (TLR-4). The objective of this study was to investigate the involvement of TLR-4 activation in the development and progression of autoimmune destructive arthritis.Methods. A naturally occurring TLR-4 antagonist, highly purified lipopolysaccharide (LPS) from Bartonella quintana, was first characterized using mouse macrophages and human dendritic cells (DCs). Mice with collagen-induced arthritis (CIA) and mice with spontaneous arthritis caused by interleukin-1 receptor antagonist (IL-1Ra) gene deficiency were treated with TLR-4 antagonist. The clinical score for joint inflammation, histologic characteristics of arthritis, and local expression of IL-1 in joints were evaluated after treatment.Results. The TLR-4 antagonist inhibited DC maturation induced by Escherichia coli LPS and cytokine production induced by both exogenous and endogenous TLR-4 ligands, while having no effect on these parameters by itself. Treatment of CIA using TLR-4 antagonist substantially suppressed both clinical and histologic characteristics of arthritis without influencing the adaptive anti-type II collagen immunity crucial for this model. Treatment with TLR-4 antagonist strongly reduced IL-1␤ expression in articular chondrocytes and synovial tissue. Furthermore, such treatment inhibited IL-1-mediated autoimmune arthritis in IL-1Ra ؊/؊ mice and protected the mice against cartilage and bone pathology.Conclusion. In the present study, we demonstrate for the first time that inhibition of TLR-4 suppresses the severity of experimental arthritis and results in lower IL-1 expression in arthritic joints. Our data suggest that TLR-4 might be a novel target in the treatment of rheumatoid arthritis.Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology associated with chronic inflammation of peripheral joints. Today it is generally accepted that proinflammatory cytokines play an important role in the pathogenesis of RA (1); however, the mechanisms of initiation and perpetuation of the inflammatory cascade in RA are still unknown.Toll-like receptors (TLRs) are a family of pattern recognition receptors that are involved in the recognition of conserved pathogen-associated molecular patterns (2). Ligand binding to TLRs initiates a signaling cascade that leads to the activation of the NF-B and interferon regulatory factor 3 transcription factors and MAPKs, which in turn promote the production of inflammatory cytokines, chemokines, and tissuedestructive enzymes and the expression of costimulatory molecules on antigen-presenting cells (APCs). These costimulatory molecules provide a second signal to T cells to initiate the adaptive immune response (3,4

Since December 2019, coronavirus disease 2019 (COVID-19) pandemic has spread from China all over the world and many COVID-19 outbreaks have been reported in long-term care facilities (LCTF). However, data on clinical characteristics and prognostic factors in such settings are scarce. We conducted a retrospective, observational cohort study to assess clinical characteristics and baseline predictors of mortality of COVID-19 patients hospitalized after an outbreak of SARS-CoV-2 infection in a LTCF. A total of 50 patients were included. Mean age was 80 years (SD, 12 years), and 24/50 (57.1%) patients were males. The overall in-hospital mortality rate was 32%. At Cox regression analysis, significant predictors of in-hospital mortality were: hypernatremia (HR 9.12), lymphocyte count < 1000 cells/µL (HR 7.45), cardiovascular diseases other than hypertension (HR 6.41), and higher levels of serum interleukin-6 (IL-6, pg/mL) (HR 1.005). Our study shows a high in-hospital mortality rate in a cohort of elderly patients with COVID-19 and hypernatremia, lymphopenia, CVD other than hypertension, and higher IL-6 serum levels were identified as independent predictors of in-hospital mortality. Given the small population size as major limitation of our study, further investigations are necessary to better understand and confirm our findings in elderly patients.

Bartonella quintana is a gram-negative microorganism that causes trench fever and chronic bacteremia. B. quintana lipopolysaccharide (LPS) was unable to induce the production of proinflammatory cytokines in human monocytes. Interestingly, B. quintana LPS is a potent antagonist of Toll-like receptor 4 (TLR4), as it inhibited both mRNA transcription and the release of tumor necrosis factor alpha, interleukin 1␤ (IL-1␤), and IL-6 by Escherichia coli LPS in human monocytes, at ratios ranging from 1,000:1 to 10:1 (B. quintana LPS to E. coli LPS). Likewise, B. quintana LPS blocked the interaction of E. coli LPS with TLR4 in transfected cell lines. The extent of the inhibitory effect of B. quintana LPS was demonstrated in microarray studies, which showed downregulation of practically all genes induced by LPS in monocytes. Because of the role of TLR4 in inflammation, B. quintana LPS may prove useful as a potent anti-TLR4 agent with therapeutic potential in both infections and autoimmune inflammation.Bartonella quintana is a gram-negative pathogen initially described during World War I as the agent of trench fever, a disease associated with recurrent fever and headaches. In the past few decades, B. quintana infection has been identified in homeless people (4). While most individuals with B. quintana infection recover, some 5 to 10% eventually develop chronic bacteremia (4) and subsequent complications, such as chronic endocarditis in the absence of preexisting heart valve lesions (20). New manifestations of B. quintana infections, such as bacillary angiomatosis, bacillary peliosis hepatitis, and chronic lymphadenopathy, have also been described (2). These manifestations have been attributed to proliferative and antiapoptotic effects of Bartonella spp. (6).A characteristic of B. quintana bacteremia is the absence of symptoms of high fever and signs of septic shock, disseminated intravascular coagulation, or organ failure. Lipopolysaccharide (LPS, or endotoxin) is a main component of the outer membranes of gram-negative microorganisms, and the LPSs from gram-negative enteric bacteria (such as Escherichia coli and Salmonella enterica) are able to induce proinflammatory cytokines, chemokines, and adhesion molecules (23) and thereby to evoke the clinical signs of sepsis. The lipid A moiety of LPS interacts with a membrane receptor complex containing Tolllike receptor 4 (TLR4), and CD14 (17,19,23). Because of strong proinflammatory effects of most species of LPS, the apparent absence of sepsis syndrome in patients with B. quintana bacteremia is a puzzling aspect of the infection. As an explanation, overproduction of the anti-inflammatory cytokine interleukin-10 (IL-10) and an attenuated inflammatory cytokine profile during B. quintana bacteremia have been proposed (5), but the molecular mechanisms have remained elusive.Recently, the LPS of the related organism Bartonella henselae was purified and characterized as a penta-acylated deep-rough LPS with low endotoxic activity (17,27). In the present study, we investigated the bio...

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In this consecutive series, diagnosis of G. lamblia infection accounted for 6.5% of patients with IBS and dyspepsia. Duodenal biopsies for diagnosis of giardiasis may be unnecessary if stool sample examination is performed.